ABSTRACT
Signals delivered to B cells via CD40 can synergize with those provided by other B cell surface receptors to induce B cell proliferation and antibody class switching as well as modulate cytokine production and cell adhesion. Recently, it has been shown that the ligand for CD40 is a cell surface protein of approximately 39 kDa expressed by activated T cells, gp39. Here we report on the isolation and characterization of a cDNA clone encoding human gp39, a type II membrane protein with homology to TNF, and the construction and characterization of a soluble recombinant form of gp39. COS cell transfectants expressing gp39 synergized with either anti-CD20 mAb or PMA to drive strong B cell proliferation and alone were able to drive B cells to proliferate weakly. In all cases the B cell proliferation induced by gp39-expressing COS cells was reduced to background levels by the addition of soluble CD40. Unlike gp39-expressing COS cells, recombinant soluble gp39 was not mitogenic alone and required co-stimulation to drive B cell proliferation. These results suggest that B cells require a second signal besides gp39-CD40 to drive proliferation and that soluble gp39 alone in a non-membrane bound form is able to provide co-stimulatory signals to B cells.
Subject(s)
Antigens, CD/metabolism , Antigens, Differentiation, B-Lymphocyte/metabolism , Membrane Proteins/metabolism , T-Lymphocytes/immunology , Tumor Necrosis Factor-alpha/genetics , Amino Acid Sequence , B-Lymphocytes/cytology , B-Lymphocytes/immunology , Base Sequence , CD40 Antigens , CD40 Ligand , Cell Division , Cell Line , Cells, Cultured , DNA , Humans , Membrane Proteins/genetics , Molecular Sequence Data , Multigene Family , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Sequence Homology, Amino Acid , T-Lymphocytes/metabolismABSTRACT
The effect of lesions on nerve growth factor receptor (NGFr) immunoreactivity (IR) in motoneurons within the mature feline trigeminal motor nucleus was investigated. Ten days following complete unilateral retrogasserian trigeminal rhizotomy including transection of the trigeminal motor root, motoneurons within the ipsilateral trigeminal motor nucleus showed NGFr-IR. In contrast, motoneurons within the contralateral trigeminal motor nucleus and within both trigeminal motor nuclei in unoperated control subjects did not show NGFr-IR. It is suggested that the appearance of NGFr-IR in motoneurons within the ipsilateral trigeminal motor nucleus after rhizotomy represents an attempts towards recovery and may be associated with the regrowth of its cut axons.
